8
M. A. Asson-Batres
discriminate between these possibilities, Fletcher and Rigdon fed one-day old Peking
ducks a defined vitamin A deficient diet, a diet supplemented with 2500 units of a
vitamin A preparation supplied by Eli Lilly & Co, or a standard Purina Duck ration
made by Ralston Purina Mills. Vitamin A deficient birds displayed muscular weakness, lack of coordination, ataxia, and paralysis after 10–15 days. The birds were
unable to walk normally and frequently fell over on their backs. Complete paralysis preceded death. Extreme buckling and twisting of the spinal cord suggested the
spinal cord was growing at a faster rate than the vertebral column, which lent support
for the view that mechanical distortion promoted neurological degeneration. However, this “…purely mechanical” view did not explain all of the results, including
the presence of numerous tumor-like masses on the surface of the spinal cord, the
transition of putative connective tissue into cartilage and bone, or the degeneration
of the myelinated fiber tracts in the spinal cord and medulla. Fletcher and Rigdon
concluded that the “problem of the effect of vitamin A deficiency on the nervous
system is not entirely settled.” (Fletcher and Rigdon 1949).
Effects of Vitamin A on Reproduction and Embryonic
Development
In the 1920s, Herbert Evans’ group reported seeing the constant appearance of cornified cells in vaginal smears of rats fed a vitamin A deficient diet and proposed using
them to assess the vitamin A status of dams. Further studies by the group led them
to conclude that vitamin A was essential for fertilization and implantation. In their
studies, female rats were fed a vitamin A deficient diet from the day of weaning until
they were 60 days of age, when wheat germ oil was introduced into the diet to assure
an adequate level of vitamin E. At 100–200 days of age, the deficient females were
paired nightly with a normal vitamin A sufficient male. Estrus and ovulation occurred
frequently, but only one-fifth of the copulations produced successful implantation.
Thirteen of 59 copulations resulted in the birth of live young (Evans 1928).
Studies designed by the Warkany laboratory in the late 40s and early 1950s also
mated vitamin A deficient females with normal vitamin A sufficient males. 75%
of the embryos produced by the deficient dams exhibited developmental anomalies
in one or more organs, including abnormal development of the eye and retina, the
kidneys and genito-urinary tract, diaphragm, aortic arches of the heart and major
arteries, and the lungs and respiratory tract. 54% of male offspring showed improper
descent of the testes. Many embryos and fetuses died in utero, as shown for example,
in one study, where only 261 of 439 inseminated females carried their conceptus
to day 20, 21, or 22 of development or birth. Restoring vitamin A to the dam and
her developing embryos at progressively earlier times during pregnancy resulted in a
progressive reduction in malformed organs, providing strong evidence that vitamin
A was essential for normal, sequential, development of embryonic organ systems
(Wilson et al. 1953).
M. A. Asson-Batres
discriminate between these possibilities, Fletcher and Rigdon fed one-day old Peking
ducks a defined vitamin A deficient diet, a diet supplemented with 2500 units of a
vitamin A preparation supplied by Eli Lilly & Co, or a standard Purina Duck ration
made by Ralston Purina Mills. Vitamin A deficient birds displayed muscular weakness, lack of coordination, ataxia, and paralysis after 10–15 days. The birds were
unable to walk normally and frequently fell over on their backs. Complete paralysis preceded death. Extreme buckling and twisting of the spinal cord suggested the
spinal cord was growing at a faster rate than the vertebral column, which lent support
for the view that mechanical distortion promoted neurological degeneration. However, this “…purely mechanical” view did not explain all of the results, including
the presence of numerous tumor-like masses on the surface of the spinal cord, the
transition of putative connective tissue into cartilage and bone, or the degeneration
of the myelinated fiber tracts in the spinal cord and medulla. Fletcher and Rigdon
concluded that the “problem of the effect of vitamin A deficiency on the nervous
system is not entirely settled.” (Fletcher and Rigdon 1949).
Effects of Vitamin A on Reproduction and Embryonic
Development
In the 1920s, Herbert Evans’ group reported seeing the constant appearance of cornified cells in vaginal smears of rats fed a vitamin A deficient diet and proposed using
them to assess the vitamin A status of dams. Further studies by the group led them
to conclude that vitamin A was essential for fertilization and implantation. In their
studies, female rats were fed a vitamin A deficient diet from the day of weaning until
they were 60 days of age, when wheat germ oil was introduced into the diet to assure
an adequate level of vitamin E. At 100–200 days of age, the deficient females were
paired nightly with a normal vitamin A sufficient male. Estrus and ovulation occurred
frequently, but only one-fifth of the copulations produced successful implantation.
Thirteen of 59 copulations resulted in the birth of live young (Evans 1928).
Studies designed by the Warkany laboratory in the late 40s and early 1950s also
mated vitamin A deficient females with normal vitamin A sufficient males. 75%
of the embryos produced by the deficient dams exhibited developmental anomalies
in one or more organs, including abnormal development of the eye and retina, the
kidneys and genito-urinary tract, diaphragm, aortic arches of the heart and major
arteries, and the lungs and respiratory tract. 54% of male offspring showed improper
descent of the testes. Many embryos and fetuses died in utero, as shown for example,
in one study, where only 261 of 439 inseminated females carried their conceptus
to day 20, 21, or 22 of development or birth. Restoring vitamin A to the dam and
her developing embryos at progressively earlier times during pregnancy resulted in a
progressive reduction in malformed organs, providing strong evidence that vitamin
A was essential for normal, sequential, development of embryonic organ systems
(Wilson et al. 1953).